Exercise during cardiac catheterization distinguishes between pulmonary and left ventricular causes of dyspnea in systemic sclerosis patients.

OBJECTIVE: The cause for shortness of breath among systemic sclerosis (SSc) patients is often lacking. We sought to characterize the hemodynamics of these patients by using simple isotonic arm exercise during cardiac catheterization. METHODS: Catheterization was performed in 173 SSc patients when resting echocardiographic pulmonary systolic pressures were <40 but >40 mmHg post stress. Patients with resting mean pulmonary arterial pressures (mPAP) ≤ 25 and pulmonary arterial wedge pressures (PAWP) ≤ 15 mmHg exercised with 1-pound hand weights. Normal exercise was defined as a change in mPAP divided by the change in cardiac output (CO) (ΔmPAP/ΔCO) ratio ≤ 2 for patients <50 years (≤3 for >50). An abnormal ΔmPAP/ΔCO ratio, an exercise transpulmonary gradient (TPG) ≥ 15, a PAWP < 20, a ΔTPG > ΔPAWP and a pulmonary vascular resistance (PVR) which increased defined exercise-induced pulmonary arterial hypertension (EIPAH). An abnormal ΔmPAP/ΔCO ratio, an exercise TPG < 15, a PAWP ≥ 20, a ΔTPG < ΔPAWP and a drop in PVR defined left ventricular diastolic dysfunction (DD). Twelve patients without SSc served as controls. RESULTS: Pulmonary pressures increased with exercise in 53 patients. Six had EIPAH and 47 had DD. With exercise, mPAP and PAWP were 20 ± 4 and 13 ± 2 in controls, 36 ± 3 and 12 ± 4 in EIPAH and 34 ± 6 and 26 ± 4 in DD. Control ΔmPAP/ΔCO was 0.8 ± 0.7, 7.5 ± 3.9 in EIPAH and 9.1 ± 7.2 in DD. Rest and exercise TPG was normal for control and DD patients but increased (12 ± 4 to 23 ± 4) in EIPAH (P < 0.0001). PVR decreased in DD but increased in EIPAH with exercise. CONCLUSIONS: Exercise during catheterization elucidates the pathophysiology of dyspnea and distinguishes EIPAH from the more common DD in SSc patients.

Survival of geriatric idiopathic pulmonary arterial hypertension patients.

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is increasingly being diagnosed in patients of advanced years. We sought to investigate observed vs expected mortality among geriatric IPAH patients treated with specific pulmonary arterial hypertension (PAH) therapy. METHODS: From the University of Connecticut's Pulmonary Vascular Disease Program database, 20 IPAH patients over 65 years of age were identified. Patient demographics, cardiopulmonary hemodynamics, PAH therapy, and mortality were retrospectively analyzed. Based on observed follow-up time, the probability of death was calculated for each subject using a prediction formula for PAH patients developed by the National Institutes of Health (NIH). Byar's method for Poisson counts was used to compare observed and expected tallies of deaths within the study sample. A P value < or = 0.05 was considered statistically significant. RESULTS: The mean age of the 20 geriatric IPAH patients was 77 years (+/- 6.6) of which 70% were female. The mean cardiopulmonary hemodynamic values for the cohort were: right atrial pressure: 10 mmHg (+/- 4); mean pulmonary artery pressure: 45 mmHg (+/- 9); pulmonary artery occlusion pressure: 11 mmHg (+/- 3); cardiac output: 4.1 L/min (+/- 1.2); cardiac index: 2.3 L/min (+/- 0.5); and pulmonary vascular resistance: 712 dynes / sec / cm-5 (+/- 319). Fourteen subjects received PAH monotherapy with bosentan, sildenafil, or epoprostenol. Six subjects received PAH combination therapy with bosentan, sildenafil, iloprost, or treprostinil. Total follow-up across the 20 subjects was 58.7 years, with average follow-up of 2.9 yrs (+/- 1.7) per subject. Based upon the NIH formula, the expected number of deaths for this cohort was 9.4. During follow-up, three deaths actually occurred. Thus, observed mortality was only 31.9% of expected (P = 0.03, 95% C.I. = [6.4%, 93.2%]). CONCLUSION: Geriatric patients are increasingly being diagnosed with IPAH. Efficacy of PAH therapy in geriatric patients is unknown. In this cohort of subjects, the outcomes of older adults treated with specific PAH therapy demonstrates improved survival relative to that predicted by the NIH formula.

Granzyme B: Correlates with protection and enhanced CTL response to influenza vaccination in older adults.

This study compared serum antibody titers and granzyme B (GrzB) levels in virus-stimulated peripheral blood mononuclear cells following influenza vaccination. Twelve of 239 older adults who subsequently developed laboratory-diagnosed influenza illness (LDI) had significantly lower GrzB levels compared to subjects without LDI (p=0.004). Eight subjects with LDI in the previous year showed an enhanced GrzB response to vaccination (p=0.02). Serum antibody titers following vaccination did not distinguish those older adults who developed LDI from those who did not. These results suggest that GrzB levels could be combined with antibody titers to more effectively predict vaccine efficacy in older adults.

The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure.

OBJECTIVES: To identify relationships between anabolic hormones, inflammatory markers, and physical function. DESIGN: Cross-sectional. SETTING: Outpatient university heart failure program in Connecticut. PARTICIPANTS: Sixty patients with an ejection fraction of 40% or less. MEASUREMENTS: The 6-minute walk distance and frailty phenotype were measured. The relationship between physical measures of hormones and inflammatory mediators were examined. Linear and ordinal logistic regression analyses were performed for the physical measures. RESULTS: Forty-three men (mean age 77 +/- 9) and 17 women (mean age 78 +/- 12) participated. Longer 6-minute walk distance was correlated with higher 25-hydroxyvitamin D (25OHD) level, and a shorter walk was correlated with higher cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), and intact parathyroid hormone (PTH) (all P<.05). Percentage of free testosterone, DHEAS alone, and N-terminal pro-brain natriuretic peptide (NTpro-BNP) did not correlate with 6-minute walk distance. Higher frailty phenotype score (more frail) was correlated with higher high-sensitivity CRP, higher IL6, and lower 25OHD levels (all P<.05). Linear regression with the 6-minute walk distance as the dependent variable and independent variables of age, sex, percentage of free testosterone, DHEAS, 25OHD, intact PTH, hsCRP, IL6, cortisol/DHEAS ratio, and NTpro-BNP, revealed age, sex, 25OHD and hsCRP to be significant (coefficient of determination=53.5%). Ordinal logistic regression with the frailty phenotype and hormonal levels revealed that age, 25OHD, and hsCRP also predicted frailty status. CONCLUSION: Twenty-five-hydroxyvitamin D and hsCRP levels may contribute to lower aerobic capacity and frailty in patients with heart failure. A longitudinal study will further define the role of 25OHD and hsCRP on muscle strength and functional decline.

Reduced exercise capacity and stress-induced pulmonary hypertension in patients with scleroderma.

OBJECTIVES: We sought to determine the incidence of stress-induced pulmonary artery (PA) systolic hypertension in a referral population of patients with scleroderma, and to examine the relation between stress-induced pulmonary systolic hypertension and exercise capacity in this population. BACKGROUND: Early detection of patients with scleroderma at risk for pulmonary hypertension (PHTN) could lead to more timely intervention and thus reduce morbidity and improve mortality. The change in PA systolic pressure (PASP) with exercise provides a possible tool for such detection. METHODS: Sixty-five patients with scleroderma (9 men and 56 women; mean age 51 +/- 12 years [SD]), normal resting PASP, and normal resting left ventricular function underwent exercise Doppler echocardiography using a standard Bruce protocol. Tricuspid regurgitation velocity was measured before and after exercise. Exercise variables including workload achieved in metabolic equivalents (METS), total exercise time, percentage of target heart rate achieved, and PASP at rest and within 60 s after exercise were recorded. RESULTS: Thirty patients (46%) demonstrated an increase in PASP to > 35 mm Hg plus an estimated right atrial pressure of 5 mm Hg. Postexercise PASP inversely correlated to both the maximum workload achieved (r = - 0.34, p = 0.006) and exercise time (r = - 0.31, p = 0.01). In women, the correlation was more significant (r = - 0.38, p = 0.003). Patients in the lowest quartile of exercise time, with the least cardiac workload achieved, produced the highest postexercise PASP. CONCLUSION: Stress-induced PHTN is common in patients with scleroderma, even when resting PASP is normal. Stress Doppler echocardiography identifies scleroderma patients with an abnormal rise in PASP during exertion. Peak PASP is linearly related to exercise time and maximum workload achieved. Measurement of PASP during exercise may prove to be a useful tool for the identification of future resting PHTN.

T cell responses are better correlates of vaccine protection in the elderly.

It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination. This study prospectively evaluated the relationship between the development of influenza illness, and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure (CHF). Adults age 60 years and older (90 subjects), and 10 healthy young adult controls received the 2003-04 trivalent inactivated influenza vaccine. Laboratory diagnosed influenza (LDI) was documented in 9 of 90 older adults. Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness (LDI subjects) and those who would not (non-LDI subjects). In contrast, PBMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects. The mean IFN-gamma:IL-10 ratio in influenza A/H3N2-stimulated PBMC was 10-fold lower in LDI vs non-LDI subjects. Pre-and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI. In non-CHF subjects with LDI, granzyme B levels increased to high levels at the time of influenza infection. In conclusion, measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people. Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults.

Treatment of metronidazole-resistant Trichomonas vaginalis with tinidazole: case reports of three patients.

Metronidazole-resistant Trichomonas vaginalis has been reported across the United States. Some reports have suggested that clinically resistant cases could be increasing. Currently, metronidazole is the only drug available to treat trichomoniasis, including resistant cases. In such cases, treatment usually consists of giving higher and more prolonged doses of metronidazole, which patients are often unable to tolerate. Tinidazole, a second-generation nitroimidazole currently under development in the United States, has been shown to be an effective therapy in resistant T. vaginalis. Tinidazole appears to have several advantages over metronidazole, including greater in vitro potency against both sensitive and resistant strains of T. vaginalis, a more prolonged duration of action, and improved patient tolerability. This report describes the successful use of tinidazole in 3 cases of clinically metronidazole-resistant trichomoniasis.

Congestive heart failure and the elderly.

As patients age, congestive heart failure becomes an increasingly important problem and accounts for up to 20% of hospital admissions for patients over 65 years. With technological improvements in the treatment of coronary artery disease, improved survival after myocardial infarction, and better hypertension therapy, patients are living longer, thus the need for successful management of older patients with chronic heart failure. The elderly, especially minorities, tend to be under-represented in congestive heart failure trials. This article will focus on the care of the geriatric patient with congestive heart failure.

Failure of benefit and early hazard of bucindolol for Class IV heart failure.

OBJECTIVES: The risks and benefits of beta-blockade with bucindolol were assessed in heart failure (HF) patients with Class IV symptoms within the Beta-blocker Evaluation of Survival Trial (BEST). BACKGROUND: beta-blockade is accepted therapy for mild to moderate HF, but its safety and efficacy in advanced HF have not been established. METHODS: BEST recruited 2708 HF patients; of these, 226 with Class IV symptoms (n=114 randomized to bucindolol, n=112 to placebo) formed the basis of this study. All-cause death, HF hospitalization, and drug discontinuations occurring early during therapy (< or =6 months) and overall during follow-up were assessed. Compared with Class III, Class IV patients were older and had higher plasma norepinephrine levels, prevalence of coronary disease, S3 gallops, and lower ejection fractions, but characteristics of the 2 Class IV treatment groups were similar. RESULTS: During a mean of 1.6 years, 49% Class IV patients died, and 54% were hospitalized for HF. Bucindolol increased the combined endpoint of death or HF hospitalization within the first 6 months (hazard ratio [HR]=1.7, 95% confidence interval [CI]=1.1-2.7) and did not result in benefit overall (HR=1.2, 95% CI=0.9-1.6). HF hospitalization alone within 6 months was increased by bucindolol (HR=1.7), and an early adverse trend for death was seen (HR=1.6) with no benefit overall (HR=1.1). Bucindolol was discontinued more frequently than placebo for worsening HF (11% versus 4%) and hypotension (3% versus 0%). CONCLUSIONS: Class IV HF patients in BEST were at high risk. Bucindolol did not reduce death or HF hospitalization and was associated with early hazard.

Guidelines for the diagnosis, treatment and prevention of postoperative infections.

Bacterial contamination of the operative site is a common occurrence in obstetrics and gynecology. The widespread use of antibiotic prophylaxis has reduced but not eliminated serious postoperative infections. For most operations, a single dose of a limited-spectrum drug has been as effective as a multidose regimen. In the differential diagnosis it is important to consider cellulitis, abscess, necrotizing fasciitis and septic pelvic thrombophlebitis. Abscess and necrotizing fasciitis are expected to require invasive therapy in addition to antibiotics, while cellulitis and septic pelvic thrombophlebitis should respond to medical management alone. Although a postoperative fever is a warning sign of possible infection, it may also be caused by the antibiotics that are given for treatment. The use of prolonged courses of antibiotics once the patient is clinically well is discouraged. While clinical guidelines are provided for use in the diagnosis and management of postoperative infections, these recommendations are intended for general direction and not as an exclusive management plan.

Left ventricular function in atrial fibrillation during overdrive pacing.

OBJECTIVE: Our purpose was to measure the effect of ventricular pacing in patients with atrial fibrillation (AF) on stroke volume and cardiac output. BACKGROUND: Unceasing variation in cycle length in AF decreases stroke volume and cardiac output. Because ventricular-inhibited pacing after atrioventricular node ablation has been reported to improve left ventricular performance, we tested the hypothesis that overdrive pacing would produce a similar benefit by regularizing cycle length. METHODS AND RESULTS: We studied 18 patients with chronic AF and permanent pacemakers. The aortic time velocity integral (TVI) was measured with continuous-wave Doppler and was used as a surrogate measure of stroke volume (stroke volume = TVI x aortic valve area, and aortic valve area is constant whether in AF or during pacing). For each patient, the linear relation between preceding cycle length and TVI in AF was used to estimate relative stroke volume (TVI compared within each patient) at a preceding cycle length of 666 ms in AF, and a similar comparison between AF and pacing was made at the minimum allowable pacing rate. Relative stroke volume in AF was then compared with relative stroke volume at both the fixed cycle (666 ms) and the minimum allowable rate. During pacing at 666 ms, relative stroke volume increased significantly by 18% (t = 2.8, P =.048), but there was no difference in cardiac output during pacing at the minimum possible rate and the corresponding preceding cycle length in AF. CONCLUSION: Our data suggest that regularization of ventricular rhythm by overdrive pacing in patients with AF only improves stroke volume (and by extension, cardiac output) at pacing rates at the outer limit of and above the normal physiologic range.